Ryuichi Iwakiri

Proportion of reflux esophagitis in 6010 Japanese adults: Prospective evaluation by endoscopy

Abstract: Compared with findings in Western countries, the prevalence of reflux esophagitis in Oriental countries is estimated to be low. In this prospective study, we aimed to examine the proportion of reflux esophagitis in Japanese adults, as evaluated by endoscopy. Endoscopists were prospectively directed to grade esophageal mucosal breaks with esophagitis according to the Los Angeles Classification of Esophagitis in all subjects that underwent endoscopic examination. In total, 6010 subjects underwent endoscopic examination for evaluation of esophagitis grading from December 1996 to February 1998. The subjects included 4394 outpatients who were not receiving medication for gastrointestinal disease and 1616 subjects who visited the hospital for routine physical examinations. The overall proportion of esophagitis was 16.3%. Most of the subjects with esophagitis were classified as having grade A or B (proportion of grades A and B, 9.6% and 4.6%, respectively). The age-related proportion of esophagitis and of severe esophagitis (i.e., grades C and D) increased in females aged over 70 and in males aged over 80. Increased body mass index (partly due to decreased height caused by osteoporosis), and/or hiatal herniation, were related to the proportion of esophagitis in females aged over 70. These data indicated that reflux esophagitis is a common disease in Japan. However, severe esophagitis (grades C and D) is not common.

Visceral fat accumulation and insulin resistance are important factors in nonalcoholic fatty liver disease

BackgroundNonalcoholic fatty liver diseases are often associated with obesity, insulin resistance, and excessive visceral fat accumulation. The aims of this study were (1) to evaluate the relationship between the severity of fatty liver and visceral fat accumulation in nonalcoholic fatty liver diseases, and (2) to investigate the relationships of fatty liver with biochemical data and insulin resistance.MethodsOne hundred twenty-nine subjects (63 women) with fatty liver diagnosed by ultrasonography were enrolled. Subjects positive for hepatitis B virus, hepatitis C virus, or autoimmune antibodies and those whose alcohol intake was over 20 g/day were excluded. The visceral fat area at the umbilical level and the liver–spleen ratio were evaluated by computed tomography.ResultsThe severity of fatty liver evaluated by ultrasonography showed a significant positive relationship with the visceral fat area and waist circumstance (fatty liver severity: mild, 92.0 ± 30.9 cm2; moderate, 122.1 ± 32.6 cm2; severe, 161.0 ± 48.4 cm2; P < 0.0001). The visceral fat area and liver–spleen ratio were negatively correlated (r = −0.605, P < 0.0001). The severity of fatty liver showed strong positive relationships with serum aspartate aminotransferase, alanine aminotransferase, fasting plasma glucose, fasting plasma insulin, and insulin resistance. The severity of fatty liver was positively related to the visceral fat area in 49 nonobese subjects (body mass index <25).ConclusionsThe severity of fatty liver was positively correlated with visceral fat accumulation and insulin resistance in both obese and nonobese subjects, suggesting that hepatic fat infiltration in nonalcoholic fatty liver disease may be influenced by visceral fat accumulation regardless of body mass index.

Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment

Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment have been produced by the Japan Gastroenterological Endoscopy Society in collaboration with the Japan Circulation Society, the Japanese Society of Neurology, the Japan Stroke Society, the Japanese Society on Thrombosis and Hemostasis and the Japan Diabetes Society. Previous guidelines from the Japan Gastroenterological Endoscopy Society have focused primarily on prevention of hemorrhage after gastroenterological endoscopy as a result of continuation ofantithrombotic therapy, without considering the associated risk of thrombosis. The new edition of the guidelines includes discussions of gastroenterological hemorrhage associated with continuation of antithrombotic therapy, as well as thromboembolism associated with withdrawal of antithrombotic therapy.

Clinical symptoms in endoscopic reflux esophagitis: evaluation in 8031 adult subjects.

This study aimed to evaluate the correlation between symptoms and endoscopic findings in reflux esophagitis. Subjects, 8031 persons without medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia, and acid regurgitation by associated medical staff before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) were classified as positive reflux esophagitis, and 2223 (27.7%) had heartburn, 1522 (19.0%) had dysphagia, 493 (6.1%) had odynophagia, and 1466 (18.3%) had acid regurgitation. Multivariate analysis indicated that the symptom most related to esophagitis was heartburn (odds ratio: 2.46), although ∼40% of subjects with grade C or D did not complain of heartburn. Regarding the other symptoms, less than 30% subjects with severe esophagitis complained of the symptoms and the odds ratio was ∼1. These results indicate that endoscopic esophagitis was not equivalent to any reflux symptoms from which subjects suffered in their daily lives.

Endoscopic closure of perforations caused by EMR in the stomach by application of metallic clips

BACKGROUND The number of complications associated with use of EMR for early-stage gastric cancer, including perforation, has increased with the increasing use of this procedure. Endoscopic clip application was performed in patients who sustained a perforation as a result of EMR for gastric neoplasm. PATIENTS AND METHODS Seven patients who underwent endoscopic application of metallic clips to close perforations were studied. The omental patch method was applied in one case with a large perforation. OBSERVATIONS In all patients, endoscopic clip application successfully closed the perforation of the stomach, which occurred after EMR. No patient required laparotomy. CONCLUSIONS The technique of endoscopic clip application might be useful for treatment of patients who sustain a perforation caused by EMR.

Risk factors for complications of endoscopic submucosal dissection in gastric tumors : analysis of 478 lesions

PurposeEndoscopic submucosal dissection (ESD) technique has facilitated en bloc removal of widely spread lesions from the stomach. This retrospective study aimed to determine factors associated with serious complications of ESD.MethodsBetween December 2001 and March 2007, we have performed ESD for 478 lesions in 436 patients. We experienced 39 patients with post-operative bleeding and 17 patients with perforation. Risk factors of patients who received ESD in gastric mucosal tumors for complications were evaluated, focusing on resected size, location, scar lesions, operation time, and experience of endoscopists. We evaluated the patients’ background characteristics including sex, age, body mass index (kg/m2), drug history of anticoagulant, and underlying diseases including cerebrovascular disorder, ischemic heart disease, liver dysfunction, renal dysfunction, hyperuricemia, hypertension and diabetes mellitus.ResultsMultivariate analysis indicated a risk factor for perforation was long operation time. Multivariate analysis indicated a significant risk factor for post-operative bleeding was size of the resected tumor.ConclusionsThis study indicated risk factors for serious complications of ESD. Large resected tumor size was a risk factor for post-operative bleeding, while long operation time was a risk factor for perforation. Information regarding operation risk factors should be useful for planning strategies for ESD.

iNOS enhances rat intestinal apoptosis after ischemia-reperfusion.

The aim of this study was to demonstrate (i) the role of iNOS (inducible nitric oxide synthase) on apoptosis in the rat intestinal mucosa after ischemia-reperfusion, and (ii) the effect of iNOS on the release of cytochrome c from mitochondria. The superior mesenteric artery was occluded for 60 min and was followed by a 60 min reperfusion. Rats were pretreated with an intraperitoneal injection of the following iNOS inhibitors: N-nitro-L-arginine methyl ester, aminoguanidine, and (1S,5S,6R,7R)-7- chloro-3-imino-5-methyl-2-azabicyclo [4. 1. 0] heptane hydrochloride (ONO-1714). Apoptosis was evaluated and NO(X) in the portal vein was assayed. The amount of iNOS, caspase-3, and cytochrome c were determined by a Western blot analysis. Intestinal mucosal epithelial mitochondrial dehydrogenase activity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoilium bromide. Ischemia-reperfusion increased intestinal mucosal apoptosis, NO(X) production in the portal vein, the amount of iNOS protein, and the release of cytochrome c, but not caspase-3. Inhibitors of iNOS significantly attenuated the induction of apoptosis, increased NO(X) production, and release of cytochrome c. Mitochondrial dysfunction was induced by ischemia-reperfusion, which was ameliorated by iNOS inhibitors. Our results indicate that iNOS is related to increased mucosal apoptosis in the rat small intestine after ischemia-reperfusion, which is partly explained by the release of cytochrome c from mitochondria to cytosols following mitochondrial dysfunction.

NSAIDs are a significant risk factor for colonic diverticular hemorrhage in elder patients: Evaluation by a case-control study

Background and Aim:  Diverticular bleeding is a common cause of lower gastrointestinal hemorrhage. Several factors, including use of non‐steroidal anti‐inflammatory drugs (NSAIDs), antithrombotic agents and arteriosclerosis, could be risk factors. The aim of this study is to identify these risk factors.

Role of Helicobacter pylori infection and nonsteroidal anti-inflammatory drug use in bleeding peptic ulcers in Japan

BackgroundHelicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known major causes of peptic ulcers. This study aimed to characterize the features of bleeding peptic ulcers in Japan.MethodsThis prospective study evaluated 116 patients revealed to have bleeding peptic ulcers from January 2000 to December 2002.ResultsEighty-eight of the 116 patients (75.9%) had H. pylori infection. Seventy (60.3%) patients were positive for H. pylori with no history of NSAID use (group A), and 18 (15.5%) were positive for H. pylori with a history of NSAID use (group B). Among the H. pylori-negative patients, 15 (12.9%) were associated with NSAID use (group C). Thirteen (11.2%) patients had no H. pylori infection or history of NSAID use (group D). Among the 33 patients with a history of NSAID use, 11 were on-demand NSAID users and 14 took daily low-dose aspirin. The patients in groups B and C were significantly older that those in groups A and D, and they more frequently had coexisting diseases compared with group A. In group D, 11 patients had atrophic changes revealed by endoscopic examination, suggesting a past H. pylori infection, and these atrophic changes remained at the time of bleeding. Many of the patients in group D had serious comorbidity. Compared with healthy control subjects, the concentrations of both phosphatidylcholine and phosphatidylethanolamine were significantly decreased in the antral gastric mucosa in all patient groups.ConclusionsNSAID use contributed to bleeding ulcers in 28.4% of patients; thus, low-dose aspirin or on-demand NSAID use may cause bleeding ulcers. There were only two (1.7%) confirmed cases of H. pylori-negative, non-NSAID ulcers.

T cell deficiency leads to liver carcinogenesis in azoxymethane-treated rats

There is an increasing amount of evidence suggesting that T cell deficiency contributes to tumor development. However, it is unclear whether T cell deficiency leads to liver and colon carcinogenesis. The aim of this study was to investigate the role of T cells on liver and colon carcinogenesis. Athymic F344/N Jcl-rnu/- (nu/nu) rats and euthymic F344/N Jcl-rnu/+ (nu/+) rats were administered the carcinogen azoxymethane (AOM) at a dose of 15 mg/kg body wt once a week for 2 weeks. At 48 weeks after the second carcinogen treatment, the rats were sacrificed, and livers and colons were examined. Apoptosis and cell proliferation were evaluated by DNA fragmentation and proliferating cell nuclear antigen assays, respectively. Wild-type p53 and members of the Jun and Fos oncogene families were detected by Western blotting. AOM treatment induced 100% liver tumor and 63.6% colon tumor incidence in T cell–deficient nu/nu rats, compared with 0% and 38.5% incidence in nu/+ rats. T cell deficiency promoted the inhibitory action of AOM on apoptosis in both liver and colon at 48 weeks. In contrast, T cell deficiency increased cell proliferation after AOM treatment in both tissues. Wild-type p53 was reduced in both tissues of T cell–deficient rats. AOM treatment induced c-Jun and c-Fos expressions in the liver but increased only Fos B in the colon, whereas T cell deficiency enhanced c-Jun overexpression in the liver. These results suggest that T cell deficiency leads to liver carcinogenesis partly by a reduction in wild-type p53 and increasing c-Jun expression in AOM-treated rats.